An analysis of genomic data from nearly 250,000 participants in the National Institutes of Health’s Research Program has identified more than 275 million previously unreported genetic variations, nearly 4 million of which have potential health consequences.
The data, reported Feb. 19 in the journal Nature, constitutes a research resource that is unprecedented in its scale and diversity, as 77% of the participants historically have been underrepresented in biomedical research, and 46% are from underrepresented racial and ethnic minorities.
“Collectively we anticipate that this work will advance the promise of precision medicine for all Americans. It is a significant step to addressing the health of the diverse population of the United States,” said the paper’s corresponding author, Alexander Bick, MD, PhD, of Vanderbilt University Medical Center.
is an historic effort to gather genomic and health data from 1 million or more people of widely diverse backgrounds. VUMC, which has pioneered studies of genetic contributions to disease and why people vary in response to medications, leads the Data and Research Center.
Historically biomedical and genomic research has represented people who are primarily of European genetic ancestry. The exclusion of large groups of people from these studies has made it difficult to obtain a comprehensive understanding of human health.
As a result, estimates of the cumulative effect of multiple genetic variants, called polygenic risk scores, may not accurately reflect the true risk for developing certain diseases in underrepresented groups.
In a companion paper published Feb. 19 in , researchers from the Electronic Medical Records and Genomics (eMERGE) Network describe how they used the Researcher Workbench to calibrate polygenic risk scores for 10 common conditions, including diabetes, heart disease and prostate cancer, in 25,000 individuals of diverse ancestry.
This robust evaluation of risk scores across multiple genetic ancestries would not have been possible without access to the richly diverse dataset, the researchers noted.
The eMERGE network was launched in 2007 by the National Human Genome Research Institute of the NIH to connect DNA biorepositories with electronic health record (EHR) systems for large scale, high-throughput genetic research.
VUMC has played a major role in eMERGE as a network site and as the national coordinating center since the network’s inception.
Recruitment of participants began in May 2018. To date, more than 500,000 participants have agreed to share their EHRs, provided physical measurements and other health-related information, and donated at least one biospecimen, such as a blood sample, for storage in one of the program’s biobanks.
Working with Verily, the life science subsidiary of Google’s parent company, Alphabet Inc., and the Broad Institute of MIT and Harvard, VUMC developed processes for cleaning, de-identifying and standardizing data collected from participants, and built tools and cloud-computing capacity to ensure the data were accessible and secure.
In 2020 the program launched the beta version of its cloud-based research platform, called Researcher Workbench. Access is open to registered researchers affiliated with institutions that have signed a data use and registration agreement with .
As of February 2024, 680 institutions had agreements in place, allowing more than 8.900 registered researchers to work on more than 8,400 projects.
In 2022, the program also began to share health-related genetic research results with participants who choose to receive them. These results include a Hereditary Disease Report and a Medicine and Your DNA report
As of January 2024, approximately 200,000 participants had been sent invitations to review their results, and about half of them have accepted. Participants who choose to receive their health-related DNA results can schedule a meeting with a genetic counselor to discuss the results.
In their conclusion, Bick and his colleagues predicted their partnership with participants will enable scientists to “move beyond large-scale genomic discovery to understanding the consequences of implementing genomic medicine at scale”—at the level of the individual.
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Bick is a leading genomic researcher and assistant professor of Medicine at VUMC. He and his VUMC co-authors, who are also principal investigators of the Data and Research Center (DRC), include:
- Melissa Basford, MBA, senior director, big data support services, Vanderbilt Institute for Clinical and Translational Research (VICTR), and genomics principal investigator for the
- Paul Harris, PhD, vice president for research informatics at VUMC, professor of Biomedical Informatics and Biostatistics, director of VICTR’s Office of Clinical Research Informatics, and corresponding principal investigator for the DRC.
- Dan Roden, MD, senior vice-president for personalized medicine at VUMC, the Sam L. Clark, MD, PhD professor of Medicine, Pharmacology, and Biomedical Informatics, and an internationally recognized pioneer in pharmacogenomics, who is co-principal investigator of the DRC.
More than 100 people from VUMC and the Meharry-Vanderbilt Alliance have contributed to , among them the following co-authors of the paper: Ashley Able, Robert Carroll, PhD, Henry Condon, Ashley Green, Jodell Linder Jackson, PhD, Kelsey Mayo, PhD, Yuanyuan Wang, PhD, and Jennifer Zhang, MS.
Sara Van Driest, MD, PhD, associate professor of Pediatrics and Medicine at VUMC, is director of pediatrics for , and Consuelo Wilkins, MD, MSCI, Senior Vice President for Health Equity and Inclusive Excellence at VUMC, directs the Engagement Core.
VUMC’s Josh Peterson, MD, MPH, is co-principal investigator of the eMERGE national coordinating center with Niall Lennon, PhD, of the Broad Institute of MIT and Harvard. Jackson, assistant director of scientific networks and genomics at VUMC, is the coordinating center’s operations director.
Roden, Digna Velez Edwards, PhD, and Wei-Qi Wei, MD, PhD, are principal investigators of VUMC’s eMERGE site. Additional eMERGE investigators at VUMC are Jennifer Below, PhD, Ellen Wright Clayton, MD, JD, QiPing Feng, PhD, Jonathan Mosley, MD, PhD, Nataraja Sarma Vaitinadin, MBBS, PhD, MPH, and Georgia Weisner, MD, MS.
